Loss of perineuronal net N-acetylgalactosamine in Alzheimer's disease

Acta Neuropathol. 2005 Oct;110(4):393-401. doi: 10.1007/s00401-005-1060-2. Epub 2005 Aug 30.


The perineuronal net (PN), a specialised region of extracellular matrix, is interposed between the neuronal cell surface and astrocytic processes. It is involved in the buffering of ions, in the development, stabilisation and remodelling of synapses and in the regulating the neuronal microenvironment particularly around the parvalbumin-positive GABAergic neurons. We have investigated the relative preservation of Wisteria floribunda agglutinin (WFA)-positive PNs and parvalbumin-positive neurons in Alzheimer's disease (AD), and the relationship of WFA-positive PNs to parenchymal tau, amyloid beta-peptide (Abeta) and MHC class II antigen (a marker of activated microglia), in paraffin sections of 100 cases with AD and 45 controls. The density of PNs that could be labelled with WFA, which binds to the N-acetylgalactosamine (GalNAc) residues of chondroitin sulphate proteoglycans, was reduced by about 2/3 in AD (P<0.001). In contrast, the density of parvalbumin-positive neurons did not differ significantly between AD and controls. Combined fluorescence imaging showed granular disintegration of WFA labelling around some parvalbumin-positive neurons. There was no significant difference in the amount of phosphorylated tau, Abeta or MHC class II antigen in areas with and without WFA-positive PNs. In AD, there is marked loss of PN GalNAc that is not topographically related to neurofibrillary pathology, parenchymal Abeta load or activated microglia. Although the parvalbumin-positive neurons themselves are relatively spared, the loss of PN GalNAc, which maintains a polyanionic microenvironment around neurons, is likely to impair the function of these inhibitory interneurons. This could in turn lead to increased activity of the glutamatergic and other neurons onto which they synapse.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylgalactosamine / metabolism*
  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / metabolism*
  • Alzheimer Disease / pathology*
  • Amyloid beta-Peptides / metabolism
  • Case-Control Studies
  • Extracellular Matrix / chemistry*
  • Extracellular Matrix / ultrastructure
  • Female
  • Humans
  • Male
  • Middle Aged
  • Nerve Net / metabolism*
  • Nerve Tissue Proteins / metabolism
  • Neurons / metabolism*
  • Neurons / pathology
  • Parvalbumins / metabolism
  • Plant Lectins / metabolism
  • Receptors, N-Acetylglucosamine / metabolism
  • tau Proteins / metabolism


  • Amyloid beta-Peptides
  • Nerve Tissue Proteins
  • Parvalbumins
  • Plant Lectins
  • Receptors, N-Acetylglucosamine
  • tau Proteins
  • wisteria lectin
  • Acetylgalactosamine